- Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity
Sauveur Michel Maira
Oncology Disease Area, Novartis Institutes for BioMedical Research, Novartis Pharma AG, CH4002 Basel, Switzerland
Mol Cancer Ther 7:1851-63. 2008
..Collectively, the preclinical data show that NVP-BEZ235 is a potent dual PI3K/mTOR modulator with favorable pharmaceutical properties. NVP-BEZ235 is currently in phase I clinical trials...
- NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations
Laboratory of Oncology Research, Medical Oncology Service, Vall d Hebron University Hospital, Barcelona, Spain
Cancer Res 68:8022-30. 2008
..In summary, NVP-BEZ235 inhibits the PI3K/mTOR axis and results in antiproliferative and antitumoral activity in cancer cells with both wild-type and mutated p110-alpha...
- Effects of torcetrapib in patients at high risk for coronary events
Philip J Barter
Heart Research Institute, Camperdown, Sydney, NSW, Australia
N Engl J Med 357:2109-22. 2007
..We investigated whether torcetrapib, a potent CETP inhibitor, might reduce major cardiovascular events. The trial was terminated prematurely because of an increased risk of death and cardiac events in patients receiving torcetrapib...
- A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis
Johnson and Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium
Science 307:223-7. 2005
..Plasma levels associated with efficacy in mice were well tolerated in healthy human volunteers. Mutants selected in vitro suggest that the drug targets the proton pump of adenosine triphosphate (ATP) synthase...
- Dihydroartemisinin-piperaquine and artemether-lumefantrine for treating uncomplicated malaria in African children: a randomised, non-inferiority trial
Barcelona Centre for International Health Research CRESIB, Hospital Clinic, Institut d Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain
PLoS ONE 4:e7871. 2009
..Dihydroartemisinin-piperaquine (DHA-PQP) is a promising fixed-dose ACT with limited information on its safety and efficacy in African children...
- Population pharmacokinetics and pharmacodynamics of piperaquine in children with uncomplicated falciparum malaria
Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Clin Pharmacol Ther 91:497-505. 2012
..025) but had significantly lower day 7 piperaquine concentrations (P = 0.024) and total piperaquine exposures (P = 0.021), suggesting that an increased dose regimen for young children should be evaluated...
- The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma
Daniel C Cho
Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
Clin Cancer Res 16:3628-38. 2010
- Artemether-lumefantrine versus dihydroartemisinin-piperaquine for falciparum malaria: a longitudinal, randomized trial in young Ugandan children
Makerere University University of California San Francisco Research Collaboration, University of California, San Francisco 94143, USA
Clin Infect Dis 49:1629-37. 2009
..However, which therapies are optimal is a matter of debate. We aimed to compare the short- and longer-term efficacy of 2 leading therapies in a cohort of young Ugandan children...
- NVP-BEZ235, a novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, elicits multifaceted antitumor activities in human gliomas
Ta Jen Liu
Department of Neuro Oncology, The University of Texas M D Anderson Cancer Center, Unit 431, 1515 Holcombe Boulevard, Houston, TX 77030
Mol Cancer Ther 8:2204-10. 2009
..These results warrant further development of NVP-BEZ235 for clinical trials for human gliomas or other advanced cancers with altered PI3K/Akt/mTOR signaling...
- Activity of the novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 against T-cell acute lymphoblastic leukemia
Department of Human Anatomy, University of Bologna, Bologna, Italy
Cancer Res 70:8097-107. 2010
- Dual targeting of phosphoinositide 3-kinase and mammalian target of rapamycin using NVP-BEZ235 as a novel therapeutic approach in human ovarian carcinoma
Division of Gynecologic Oncology, Departments of Obstetrics and Gynecology, UCLA David Geffen School of Medicine, Los Angeles, CA 90095 1740, USA
Clin Cancer Res 17:2373-84. 2011
..This study evaluates the effect of dual PI3K and mTOR inhibition using NVP-BEZ235 in preclinical models of ovarian cancer as a potential novel therapeutic strategy...
- Inhibition of metastasis in a castration resistant prostate cancer model by the quinoline-3-carboxamide tasquinimod (ABR-215050)
Sahlgrenska Cancer Center, Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Box 425, 40530 Goteborg, Sweden
Prostate 72:913-24. 2012
..Its mechanism of action is not fully elucidated, but previous studies show anti-angiogenic effects and strong interaction with the S100A9 protein...
- Declining responsiveness of Plasmodium falciparum infections to artemisinin-based combination treatments on the Kenyan coast
Kenya Medical Research Institute Wellcome Trust Research Programme, Kilifi, Kenya
PLoS ONE 6:e26005. 2011
..The emergence of artemisinin-resistant P. falciparum malaria in South-East Asia highlights the need for continued global surveillance of the efficacy of artemisinin-based combination therapies...
- Dual inhibition of PI3K and mTORC1/2 signaling by NVP-BEZ235 as a new therapeutic strategy for acute myeloid leukemia
Institut Cochin, Universite Paris Descartes, CNRS UMR8104 INSERM U1016 Service d Hématologie Biologique, Hopital Cochin, AP HP, Paris, France
Clin Cancer Res 16:5424-35. 2010
..We therefore tested, in this study, the antileukemic activity of the dual PI3K/mTOR ATP-competitive inhibitor NVP-BEZ235 compound (Novartis)...
- Efficacy and safety of dihydroartemisinin-piperaquine for treatment of uncomplicated Plasmodium falciparum malaria in endemic countries: meta-analysis of randomised controlled studies
School of Postgraduate Studies and Research, International Medical University, Kuala Lumpur 57000, Malaysia
Trans R Soc Trop Med Hyg 107:65-73. 2013
..The better safety profile of DP and once-daily dosage improves adherence and its fixed co-formulation ensures that both drugs are taken together. Our conclusion is that DP has the potential to become a first-line antimalarial drug...
- S6K1 and 4E-BP1 are independent regulated and control cellular growth in bladder cancer
Department of Urology, Klinikum rechts der Isar der Technischen Universitat Munchen, Munich, Germany
PLoS ONE 6:e27509. 2011
..Our data suggest that 4E-BP1 is a potential new target molecule and stratification marker for anti cancer therapy in UC and support the consideration of a multi-targeting approach against PI3K, mTORC1/2 and MAPK...
- Diarylquinolines are bactericidal for dormant mycobacteria as a result of disturbed ATP homeostasis
Departments of Antimicrobial Research and Functional Genomics, Johnson and Johnson, Turnhoutseweg 30, B 2340 Beerse, Belgium
J Biol Chem 283:25273-80. 2008
- Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235
Pieter J A Eichhorn
Medical Oncology Program, Vall d Hebron Institut de Oncologia, Barcelona, Spain
Cancer Res 68:9221-30. 2008
..Our data show that deregulation of the PI3K pathway, either through loss-of-function mutations in PTEN or dominant activating mutations in PIK3CA, leads to lapatinib resistance, which can be effectively reversed by NVP-BEZ235...
- Crosstalk between the PI3K/mTOR and MEK/ERK pathways involved in the maintenance of self-renewal and tumorigenicity of glioblastoma stem-like cells
Department of Molecular Cancer Science Yamagata University School of Medicine, Yamagata, Japan
Stem Cells 28:1930-9. 2010
..Thus, combinational disruption of these pathways would be a rational and effective strategy in the treatment of glioblastoma...
- Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis
Susan E Dorman
Johns Hopkins University Center for Tuberculosis Research, Baltimore, Maryland 21231, USA
Am J Respir Crit Care Med 180:273-80. 2009
..Moxifloxacin has potent activity against Mycobacterium tuberculosis in vitro and in a mouse model of antituberculosis (TB) chemotherapy, but data regarding its activity in humans are limited...
- ARQ 197, a novel and selective inhibitor of the human c-Met receptor tyrosine kinase with antitumor activity
Boston Biomedical, Inc, Norwood, Massachusetts, USA
Mol Cancer Ther 9:1544-53. 2010
..Cumulatively, these data suggest that ARQ 197, currently in phase II clinical trials, is a promising agent for targeting cancers in which c-Met-driven signaling is important for their survival and proliferation...
- The dual PI3K/mTOR inhibitor NVP-BEZ235 induces tumor regression in a genetically engineered mouse model of PIK3CA wild-type colorectal cancer
Division of Gastroenterology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts, United States of America
PLoS ONE 6:e25132. 2011
..To examine the in vitro and in vivo efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type colorectal cancer (CRC)...
- Increased AKT S473 phosphorylation after mTORC1 inhibition is rictor dependent and does not predict tumor cell response to PI3K/mTOR inhibition
Novartis Pharma AG, Novartis Institutes for BioMedical Research, Oncology, Basel, Switzerland
Mol Cancer Ther 8:742-53. 2009
..However, reduced cell viability could not be predicted from biochemical or cellular responses to mTORC1 inhibitors. These data could have implications for the clinical application of phosphatidylinositol 3-kinase/mTOR inhibitors...
- Phase I trial of a selective c-MET inhibitor ARQ 197 incorporating proof of mechanism pharmacodynamic studies
Timothy A Yap
Royal Marsden National Health Service Foundation Trust, The Institute of Cancer Research, Sutton, Surrey, UK
J Clin Oncol 29:1271-9. 2011
..A phase I trial of ARQ 197 was conducted to assess safety, tolerability, and target inhibition, including intratumoral c-MET signaling, apoptosis, and angiogenesis...
- Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrate-resistant prostate cancer
Roswell Park Cancer Institute, Buffalo, NY 14263 0001, USA
J Clin Oncol 29:4022-8. 2011
..The activity of the novel antitumor agent tasquinimod (TASQ) with S100A9 as a molecular target was investigated in men with metastatic castration-resistant prostate cancer (CRPC) and minimal symptoms...
- Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells
L L Remsing Rix
Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
Leukemia 23:477-85. 2009
..Finally, bosutinib is the first kinase inhibitor shown to target CAMK2G, recently implicated in myeloid leukemia cell proliferation...
- The diarylquinoline TMC207 for multidrug-resistant tuberculosis
Andreas H Diacon
Centre for Clinical Tuberculosis Research, the Department of Science and Technology, Faculty of Health Sciences, University of Stellenbosch, Tygerberg, all in South Africa
N Engl J Med 360:2397-405. 2009
..TMC207 potently inhibits drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro and shows bactericidal activity in patients who have drug-susceptible pulmonary tuberculosis...
- Q-VD-OPh, a broad spectrum caspase inhibitor with potent antiapoptotic properties
T M Caserta
Department of Physiology and Biophysics, Wright State University School of Medicine, Dayton, Ohio 45435, USA
Apoptosis 8:345-52. 2003
..Our data indicate that the specificity, effectiveness, and reduced toxicity of caspase inhibitors can be significantly enhanced using carboxyterminal o-phenoxy groups and may have important uses in vivo...
- Dual phosphoinositide 3-kinase/mammalian target of rapamycin blockade is an effective radiosensitizing strategy for the treatment of non-small cell lung cancer harboring K-RAS mutations
Division of Hematology and Oncology, Simmons Comprehensive Cancer Center, and Hamon Center for Therapeutic Oncology Research, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas TX 75390, USA
Cancer Res 69:7644-52. 2009
..These findings may have general applicability in cancer therapy, because aberrant activation of PI3K occurs frequently in human cancer...
- NVP-BEZ235 as a new therapeutic option for sarcomas
Maria C Manara
Laboratorio di Ricerca Oncologica, Istituto Ortopedico Rizzoli, Bologna, Italy
Clin Cancer Res 16:530-40. 2010
..To evaluate the in vitro and in vivo effects of NVP-BEZ235, a dual pan-phosphoinositide 3-kinase-mammalian target of rapamycin inhibitor in the three most common musculoskeletal tumors (osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma)...
- Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells
Saskia M Brachmann
Novartis Institutes for BioMedical Research, Oncology Disease Area, CH 4002 Basel, Switzerland
Proc Natl Acad Sci U S A 106:22299-304. 2009
..Overall, this study will provide guidance for patient stratification for forthcoming breast cancer phase II trials for NVP-BEZ235...
- Pleiotropic effects of pitavastatin
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montréal IRCM and University of Montréal, QC, Canada
Br J Clin Pharmacol 73:518-35. 2012
..It is concluded that the diverse pleiotropic actions of pitavastatin may contribute to reducing cardiovascular morbidity and mortality beyond that achieved through LDL-C reduction...
- Safety and efficacy of dihydroartemisinin-piperaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Zambian children
Department of Clinical Sciences, Tropical Disease Research Center, P, O Box 71769, Ndola Zambia
Malar J 10:50. 2011
..In 2002, the first-line treatment for uncomplicated malaria was changed to artemether-lumefantrine (AL) that has proved to be highly efficacious against multidrug resistant Plasmodium falciparum...
- A trial of combination antimalarial therapies in children from Papua New Guinea
Harin A Karunajeewa
School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, Australia
N Engl J Med 359:2545-57. 2008
..Malaria control is difficult where there is intense year-round transmission of multiple plasmodium species, such as in Papua New Guinea...
- G protein-coupled receptor 30 (GPR30) mediates gene expression changes and growth response to 17beta-estradiol and selective GPR30 ligand G-1 in ovarian cancer cells
Departments of Pharmaco Biology and Cell Biology, University of Calabria, 87030 Rende Cosenza, Italy
Cancer Res 67:1859-66. 2007
- Population pharmacokinetics of dihydroartemisinin and piperaquine in pregnant and nonpregnant women with uncomplicated malaria
Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Antimicrob Agents Chemother 56:1997-2007. 2012
..The clinical impact of these pharmacokinetic findings in pregnant women with uncomplicated malaria needs to be evaluated in larger series...
- Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition
Anthony C Faber
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA
Proc Natl Acad Sci U S A 106:19503-8. 2009
..These data indicate simultaneous inhibition of PI3K-mTOR and MEK signaling is an effective strategy for treating EGFR mutant lung cancers, including those with acquired resistance to EGFR TKIs...
- The novel orally bioavailable inhibitor of phosphoinositol-3-kinase and mammalian target of rapamycin, NVP-BEZ235, inhibits growth and proliferation in multiple myeloma
Department of Hematology and Oncology Medizinische Klinik Innenstadt, Klinikum der Universitat Munchen, Germany
Exp Cell Res 315:485-97. 2009
..Taken together, inhibition of PI3 kinase/mTOR by NVP-BEZ235 is highly effective and NVP-BEZ235 represents a potential new candidate for targeted therapy in multiple myeloma...
- In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl+ neoplastic cells
Department of Clinical Medicine, S Gerardo Hospital University of Milano Bicocca, Monza, Italy
Cancer Res 66:11314-22. 2006
..Modeling considerations attribute the superior activity of SKI-606 to its ability to bind a conformation of Bcr-Abl different from imatinib...
- Safety and efficacy of dihydroartemisinin-piperaquine in falciparum malaria: a prospective multi-centre individual patient data analysis
Shoklo Malaria Research Unit, Mae Sot, Thailand
PLoS ONE 4:e6358. 2009
..Comparator drugs were mefloquine-artesunate (MAS3) in Thailand, Myanmar, Laos and Cambodia; artemether-lumefantrine in Uganda; and amodiaquine+sulfadoxine-pyrimethamine and artesunate+amodiaquine in Rwanda...
- Preferential binding of a G-quadruplex ligand to human chromosome ends
LRP, DRR, CEA 92265, Fontenay aux Roses, France
Nucleic Acids Res 33:4182-90. 2005
..They support the hypothesis that G-quadruplex ligands induce and/or stabilize G-quadruplex structures at telomeres of human cells...
- Phase I dose-escalation study and biomarker analysis of E7080 in patients with advanced solid tumors
Department of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan
Clin Cancer Res 17:2528-37. 2011
..This Phase I study investigated maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK), pharmacodynamics (PD), and efficacy in patients with advanced solid tumors...
- Tasquinimod (ABR-215050), a quinoline-3-carboxamide anti-angiogenic agent, modulates the expression of thrombospondin-1 in human prostate tumors
Active Biotech AB, Box 724, 22007 Lund, Sweden
Mol Cancer 9:107. 2010
..The array data were validated by real-time semiquantitative reversed transcriptase polymerase chain reaction (sqRT-PCR) and protein expression techniques...
- Novel phosphoinositide 3-kinase/mTOR dual inhibitor, NVP-BGT226, displays potent growth-inhibitory activity against human head and neck cancer cells in vitro and in vivo
Kwang Yu Chang
Institute of Clinical Medicine, Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China
Clin Cancer Res 17:7116-26. 2011
..To develop a new treatment, we investigated the effect of a novel dual PI3K/mTOR inhibitor, NVP-BGT226 (BGT226), in head and neck cancer cells...
- A phase I dose-escalation study of Tivantinib (ARQ 197) in adult patients with metastatic solid tumors
Lee S Rosen
UCLA Division of Hematology Oncology, Los Angeles, CA 90404, USA
Clin Cancer Res 17:7754-64. 2011
..This open-label, phase I, dose-escalation study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of tivantinib in patients with advanced or metastatic solid tumors refractory to standard therapy...
- Tasquinimod prevents the angiogenic rebound induced by fractionated radiation resulting in an enhanced therapeutic response of prostate cancer xenografts
Susan L Dalrymple
Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Prostate 72:638-48. 2012
- Randomized, open-label trial of primaquine against vivax malaria relapse in Indonesia
Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
Antimicrob Agents Chemother 57:1128-35. 2013
..Antirelapse therapy with primaquine begun a month after treatment of the acute attack with dihydroartemisinin-piperaquine proved safe and highly efficacious against relapse by P. vivax acquired in Papua, Indonesia...
- Activity of a novel, dual PI3-kinase/mTor inhibitor NVP-BEZ235 against primary human pancreatic cancers grown as orthotopic xenografts
Division of Applied Molecular Oncology, Department of Medical Oncology and Hematology, Ontario Cancer Institute Princess Margaret Hospital, University of Toronto, Ontario, Canada
Br J Cancer 100:1267-76. 2009
..These results predict that agents targeting the PI3K/Akt/mTor pathway might have anticancer activity in pancreatic cancer patients, and support the testing of combination studies involving chemotherapy or other molecular targeted agents...
- A phase I study of E7080, a multitargeted tyrosine kinase inhibitor, in patients with advanced solid tumours
D S Boss
Division of Medical Oncology, Department of Clinical Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands
Br J Cancer 106:1598-604. 2012
- MvfR, a key Pseudomonas aeruginosa pathogenicity LTTR-class regulatory protein, has dual ligands
Department of Surgery, Harvard Medical School, Massachusetts General Hospital, USA
Mol Microbiol 62:1689-99. 2006
..These results uncover a novel biological role for HHQ; and provide novel insights on MvfR activation that may aid in the development of therapies that prevent or treat P. aeruginosa infections in humans...
- Inhibition of tumor cell growth, invasion, and metastasis by EXEL-2880 (XL880, GSK1363089), a novel inhibitor of HGF and VEGF receptor tyrosine kinases
Exelixis, Inc, South San Francisco, California 94083, USA
Cancer Res 69:8009-16. 2009
..Collectively, these data indicate that EXEL-2880 may prevent tumor growth through a direct effect on tumor cell proliferation and by inhibition of invasion and angiogenesis mediated by HGF and VEGF receptors...
- Effect of intensive statin therapy on regression of coronary atherosclerosis in patients with acute coronary syndrome: a multicenter randomized trial evaluated by volumetric intravascular ultrasound using pitavastatin versus atorvastatin (JAPAN-ACS [Japan
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan
J Am Coll Cardiol 54:293-302. 2009
- Vertical targeting of the phosphatidylinositol-3 kinase pathway as a strategy for treating melanoma
Saadia A Aziz
Department of Pathology, Yale University School of Medicine, Yale Cancer Center, New Haven, Connecticut 06510, USA
Clin Cancer Res 16:6029-39. 2010
..Phosphatidylinositol-3 kinase (PI3K) is an important target in melanoma; however, activity of PI3K inhibitors (PI3KI) is limited. Our purpose was to assess mTOR as a cotarget for PI3K...
- Pharmacokinetics of the antimalarial drug piperaquine in healthy Vietnamese subjects
Trong Chinh Nguyen
Department of Infectious Diseases, Central Military Hospital 108, Hanoi, Vietnam
Am J Trop Med Hyg 79:620-3. 2008
..Piperaquine AUC was proportional to the two doses tested and a moderate-fat meal enhanced the bioavailability of piperaquine by 41%, which should improve the therapeutic efficacy of this drug...
- Antimyeloma activity of the orally bioavailable dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235
Douglas W McMillin
Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
Cancer Res 69:5835-42. 2009
..g., dexamethasone and doxorubicin) or novel (e.g., bortezomib) anti-MM agents showed lack of antagonism. These results indicate that BEZ235 merits clinical testing, alone and in combination with other agents, in MM...
- A phase I study of foretinib, a multi-targeted inhibitor of c-Met and vascular endothelial growth factor receptor 2
Joseph Paul Eder
Early Drug Development Center, Department of Medical Oncology, Dana Farber Cancer Institute and Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, USA
Clin Cancer Res 16:3507-16. 2010
..Secondary objectives included evaluation of plasma pharmacokinetics, long-term safety after repeated administration, preliminary antitumor activity, and pharmacodynamic activity...
- Adverse pregnancy outcomes in an area where multidrug-resistant plasmodium vivax and Plasmodium falciparum infections are endemic
Jeanne Rini Poespoprodjo
District Health Authority, School of Health Research National Institute of Health Research and Development Malaria Research Program, Indonesia
Clin Infect Dis 46:1374-81. 2008
..Plasmodium falciparum infection exerts a considerable burden on pregnant women, but less is known about the adverse consequences of Plasmodium vivax infection...
- Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib
Jorge E Cortes
M D Anderson Cancer Center, Houston, TX, USA
Blood 118:4567-76. 2011
..These data suggest bosutinib is effective and tolerable in patients with chronic phase imatinib-resistant or imatinib-intolerant CML. This trial was registered at http://www.clinicaltrials.gov as NCT00261846...
- Effects of cysteinyl leukotrienes in small human bronchus and antagonist activity of montelukast and its metabolites
Laboratory of Pharmacology, EA 2070, Faculty of Medicine, Reims, France
Clin Exp Allergy 33:887-94. 2003
..Montelukast (MK), a specific CysLT1 receptor antagonist, is metabolized in two main hydroxylated metabolites (termed M5 and M6, respectively)...
- A role for cysteinyl leukotrienes in airway remodeling in a mouse asthma model
William R Henderson
Departments of Medicine and Pathology, University of Washington, Seattle, Washington 98195 6523, USA
Am J Respir Crit Care Med 165:108-16. 2002
..These data suggest an important role for cysteinyl leukotrienes in the pathogenesis of chronic allergic airway inflammation with fibrosis...
- Targeting melanoma with dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors
Department of Biomedicine, University of Basel, Mattenstrasse 28, CH 4058 Basel, Switzerland
Mol Cancer Res 7:601-13. 2009
..Based on the above results, NVP-BEZ235, which has entered phase I/II clinical trials in patients with advanced solid tumors, has a potential in metastatic melanoma therapy...
- Pharmacokinetics, safety, and tolerability of ascending single doses of moxifloxacin, a new 8-methoxy quinolone, administered to healthy subjects
Pharma Research Center, Institute of Clinical Pharmacology, Bayer AG, 42096 Wuppertal, Germany
Antimicrob Agents Chemother 42:2060-5. 1998
..The pharmacokinetic parameters derived from compartmental and noncompartmental analyses were in good agreement. The kinetics could be described best by fitting the data to a two-compartment body model...
- Inhibition profiles of phosphatidylinositol 3-kinase inhibitors against PI3K superfamily and human cancer cell line panel JFCR39
Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3 10 6, Ariake, Koto ku, Tokyo 135 8550, Japan
Eur J Cancer 46:1111-21. 2010
..The biological implication of the difference in molecular target specificity of these PI3K inhibitors is under investigation...
- The combination of RAD001 and NVP-BEZ235 exerts synergistic anticancer activity against non-small cell lung cancer in vitro and in vivo
Cheng Xiong Xu
Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, Georgia, United States of America
PLoS ONE 6:e20899. 2011
..Taken together, our results suggest that the combination of RAD001 and BEZ235 is a novel strategy for cancer therapy...
- Synergistic action of a RAF inhibitor and a dual PI3K/mTOR inhibitor in thyroid cancer
Cancer Biology Division, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA
Clin Cancer Res 17:6482-9. 2011
..We tested a novel drug combination targeting RAF, phosphoinositide 3-kinase (PI3K), and mTOR, plus VEGFR2 and RET, in thyroid cancer preclinical models with defined genetic backgrounds...
- Population pharmacokinetics of piperaquine after two different treatment regimens with dihydroartemisinin-piperaquine in patients with Plasmodium falciparum malaria in Thailand
Department of Pharmacology, Sahlgrenska Academy at Goteborg University, Goteborg, Sweden
Antimicrob Agents Chemother 52:1052-61. 2008
..Our data lend further support to a simplified once-daily treatment regimen to improve treatment adherence and efficacy and indicate that weight-adjusted piperaquine doses in children may need to be higher than in adults...
- Population pharmacokinetics of piperaquine in adults and children with uncomplicated falciparum or vivax malaria
Te Yu Hung
Medicine Unit Fremantle Hospital and Pharmacology Unit Queen Elizabeth 2 Medical Centre, School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia
Br J Clin Pharmacol 57:253-62. 2004
..To study the population pharmacokinetics of piperaquine after co-administration with dihydroartemisinin in uncomplicated malaria...
- An open-label, randomised study of dihydroartemisinin-piperaquine versus artesunate-mefloquine for falciparum malaria in Asia
National Institute of Malaria Research, Delhi, India
PLoS ONE 5:e11880. 2010
..The aim of this study was to show non-inferiority of DHA/PQP vs. artesunate-mefloquine (AS+MQ) in Asia...
- A randomized trial to monitor the efficacy and effectiveness by QT-NASBA of artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment and transmission control of uncomplicated Plasmodium falciparum malaria in western Kenya
Petra F Mens
Koninklijk Instituut voor de Tropen KIT Royal Tropical Institute, KIT Biomedical Research, Amsterdam, The Netherlands
Malar J 7:237. 2008
- Piperaquine: a resurgent antimalarial drug
Timothy M E Davis
Medicine Unit Fremantle and Pharmacology Unit Nedlands, School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia
Drugs 65:75-87. 2005
..The tolerability, efficacy, pharmacokinetic profile and low cost of piperaquine make it a promising partner drug for use as part of an ACT...
- Randomized head-to-head comparison of pitavastatin, atorvastatin, and rosuvastatin for safety and efficacy (quantity and quality of LDL): the PATROL trial
Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan
Circ J 75:1493-505. 2011
..This is the first prospective randomized multi-center trial to compare these strong statins (UMIN Registration No: 000000586)...
- Oral montelukast in acute asthma exacerbations: a randomised, double-blind, placebo-controlled trial
Crichton F Ramsay
Department of Respiratory Medicine, Norfolk and Norwich University Hospital, Norwich, UK
Thorax 66:7-11. 2011
..Although leukotriene receptor antagonists have an established role in the management of patients with chronic asthma, their efficacy in an acute asthma exacerbation is not fully known...
- Comparative long-term efficacy and tolerability of pitavastatin 4 mg and atorvastatin 20-40 mg in patients with type 2 diabetes mellitus and combined (mixed) dyslipidaemia
Department of Internal Diseases, Diabetology and Nephrology, Medical University of Silesia, Zabrze, Poland
Diabetes Obes Metab 13:1047-55. 2011
..To compare the long-term efficacy and safety of pitavastatin with atorvastatin in patients with type 2 diabetes and combined (mixed) dyslipidaemia...
- Effect of single nucleotide polymorphisms in cytochrome P450 isoenzyme and N-acetyltransferase 2 genes on the metabolism of artemisinin-based combination therapies in malaria patients from Cambodia and Tanzania
Eva Maria Staehli Hodel
Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland
Antimicrob Agents Chemother 57:950-8. 2013
..data need not be included in appropriate first-line treatments with the current artemisinin derivatives and quinolines for uncomplicated malaria in specific populations...
- Synthesis and in vivo evaluation of [11C]tariquidar, a positron emission tomography radiotracer based on a third-generation P-glycoprotein inhibitor
Department of Medicinal Chemistry, University of Vienna, Austria
Bioorg Med Chem 18:5489-97. 2010
..Our data suggest that [(11)C]-1 interacts specifically with P-gp and BCRP in the BBB. However, further investigations are needed to assess if [(11)C]-1 behaves in vivo as a transported or a non-transported inhibitor...
- Pulsed moxifloxacin for the prevention of exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial
Division of Pulmonary, Critical Care and Sleep Medicine, University of Buffalo, State University of New York, Buffalo, NY, USA
Respir Res 11:10. 2010
..This proof-of-concept study evaluates whether intermittent pulsed moxifloxacin treatment could reduce the frequency of these exacerbations...
- Vaccine adjuvant activity of 3M-052: an imidazoquinoline designed for local activity without systemic cytokine induction
3M Drug Delivery Systems, 3M Center, St Paul, MN 55144, USA
Vaccine 29:5434-42. 2011
..Given subcutaneously, 3M-052 drives a strong Th1 response to hemagglutinin and serum neutralization of viable H1N1 A/Puerto Rico/8/34 virus in the absence of circulating TNFα or the induction of Th1 cytokines...
- Residual antimalarial concentrations before treatment in patients with malaria from Cambodia: indication of drug pressure
Eva Maria Hodel
Swiss Tropical Institute, Basel, Switzerland
J Infect Dis 202:1088-94. 2010
..There is a highly diverse market for antimalarials in this area, and improved knowledge of drug pressure would be useful to target interventions aimed at reducing inappropriate drug use...
- Antitumor activity and safety of tivozanib (AV-951) in a phase II randomized discontinuation trial in patients with renal cell carcinoma
Dmitry A Nosov
Blokhin Oncology Research Center, Russia
J Clin Oncol 30:1678-85. 2012
..The antitumor activity and safety of tivozanib, which is a potent and selective vascular endothelial growth factor receptor-1, -2, and -3 inhibitor, was assessed in patients with advanced/metastatic renal cell carcinoma (RCC)...
- Simultaneous targeting of PI3K and mTOR with NVP-BGT226 is highly effective in multiple myeloma
Abteilung Hämatologie und Onkologie, Medizinische Klinik, Campus Innenstadt, Klinikum der Universitat Munchen, Munchen, Germany
Anticancer Drugs 23:131-8. 2012
..Overall, inhibition of phosphoinositol-3-kinase/mammalian target of rapamycin by NVP-BGT226 is highly effective, and NVP-BGT226 represents a potential new candidate for targeted therapy in multiple myeloma...
- Adding moxifloxacin is associated with a shorter time to culture conversion in pulmonary tuberculosis
J Y Wang
Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
Int J Tuberc Lung Dis 14:65-71. 2010
..To investigate whether adding moxifloxacin (MXF) to the standard anti-tuberculosis regimen can shorten the time to sputum culture conversion in pulmonary tuberculosis (PTB)...
- Safety profile of the respiratory fluoroquinolone moxifloxacin: comparison with other fluoroquinolones and other antibacterial classes
Francoise Van Bambeke
Unité de pharmacologie cellulaire et moléculaire and Centre de Pharmacie Clinique, Louvain Drug Research Institute, Universite Catholique de Louvain, Brussels, Belgium
Drug Saf 32:359-78. 2009
- New susceptibility breakpoints for first-line antituberculosis drugs based on antimicrobial pharmacokinetic/pharmacodynamic science and population pharmacokinetic variability
Division of Infectious Diseases, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 9113, USA
Antimicrob Agents Chemother 54:1484-91. 2010
..With the proposed breakpoints, the rates of multidrug-resistant tuberculosis could become 4-fold higher than currently assumed...
- Pitavastatin induces PON1 expression through p44/42 mitogen-activated protein kinase signaling cascade in Huh7 cells
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko cho, Nankoku, Kochi 783 8505, Japan
Atherosclerosis 202:439-45. 2009
..Furthermore, we speculate that pitavastatin affects both the phosphorylation of SREBP-2 and the Sp1 binding to PON1 DNA through the activation of p44/42 MAP kinase signaling cascade...
- Pitavastatin improves plasma pentraxin 3 and arterial stiffness in atherosclerotic patients with hypercholesterolemia
Department of Internal Medicine, JA Gifu Tohno Kousei Hospital, Gifu, Japan
J Atheroscler Thromb 16:490-500. 2009
..To investigate the effect of pitavastatin on asymptomatic atherosclerosis in patients with hypercholesterolemia...
- ATR contributes to telomere maintenance in human cells
CEA DSV iRCM SCSR, Laboratoire de Radiopathologie, INSERM Université Paris VII U967, 92265 Fontenay aux Roses, France
Nucleic Acids Res 38:2955-63. 2010
..Altogether, these data reveal that ATR plays a critical role in telomere maintenance during and/or after telomere replication in human cells...
- Highly effective therapy for maternal malaria associated with a lower risk of vertical transmission
J R Poespoprodjo
District Health Authority, Timika, Indonesia
J Infect Dis 204:1613-9. 2011
..The epidemiology of congenital malaria was investigated in a hospital-based malaria surveillance study in Papua, Indonesia...
- A randomized intervention of montelukast for post-bronchiolitis: effect on eosinophil degranulation
Chang Keun Kim
Department of Pediatrics and Asthma and Allergy Center, Inje University Sanggye Paik Hospital, Seoul, Korea
J Pediatr 156:749-54. 2010
..To investigate the effect of montelukast on eosinophil degranulation and recurrent wheezing episodes in post-respiratory syncytial virus (RSV) bronchiolitis...
- Targeting neonatal ischemic brain injury with a pentapeptide-based irreversible caspase inhibitor
Theraptosis Research Laboratory, THERAPTOSIS SA, Pasteur Biotop, Institut Pasteur, Paris 75015, France
Cell Death Dis 2:e203. 2011
..Safety pharmacology investigations, and toxicology studies in rodent and canine neonates, suggest that TRP601 is a lead compound for further drug development to treat ischemic brain damage in human newborns...
- Fluorescence intercalator displacement assay for screening G4 ligands towards a variety of G-quadruplex structures
Phong Lan Thao Tran
University of Bordeaux, ARNA Laboratory, Bordeaux, France
Biochimie 93:1288-96. 2011
..Most compounds showed a good G4 vs duplex selectivity but exhibited little, if any, specificity for one quadruplex sequence over the others. The quest for the "perfect" specific G4 ligand is not over yet!..
- A chemotype that inhibits three unrelated pathogenic targets: the botulinum neurotoxin serotype A light chain, P. falciparum malaria, and the Ebola filovirus
Faculty of Chemistry, University of Belgrade, Studentski trg 16, PO Box 51, 11158 Belgrade, Serbia
J Med Chem 54:1157-69. 2011
..Finally, the 1,7-DAAC-based derivatives were examined for Ebola filovirus inhibition in an assay employing Vero76 cells, and three provided promising antiviral activities and acceptably low toxicities...
- Drug-drug interactions with statins: will pitavastatin overcome the statins' Achilles' heel?
Department of Pharmacological Sciences, University of Milan, Italy
Curr Med Res Opin 27:1551-62. 2011
- A pharmacodynamic study of docetaxel in combination with the P-glycoprotein antagonist tariquidar (XR9576) in patients with lung, ovarian, and cervical cancer
Ronan J Kelly
Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA
Clin Cancer Res 17:569-80. 2011
..Here we report the results of a pharmacokinetic and pharmacodynamic trial using a third-generation, potent, noncompetitive inhibitor of Pgp, tariquidar (XR9576), in combination with docetaxel...
- Piperaquine resistance is associated with a copy number variation on chromosome 5 in drug-pressured Plasmodium falciparum parasites
Richard T Eastman
Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA
Antimicrob Agents Chemother 55:3908-16. 2011
..Transgene expression studies are underway with individual genes in this segment to evaluate their contribution to piperaquine resistance...
- Pharmacokinetics of dihydroartemisinin and piperaquine in pregnant and nonpregnant women with uncomplicated falciparum malaria
Marcus J Rijken
Shoklo Malaria Research Unit, PO Box 46 Mae Sot, Tak 63110, Thailand
Antimicrob Agents Chemother 55:5500-6. 2011
..However, a more detailed analysis using population pharmacokinetic modeling is needed to fully investigate the differences found for some of the pharmacokinetic parameters, such as the terminal half-life...
- In vitro activities of piperaquine, lumefantrine, and dihydroartemisinin in Kenyan Plasmodium falciparum isolates and polymorphisms in pfcrt and pfmdr1
Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, Kilifi, Kenya
Antimicrob Agents Chemother 53:5069-73. 2009
..Therefore, the use of LM-artemether is likely to lead to the selection of more CQ-susceptible parasites...
- Pharmacokinetics and bioequivalence evaluation of two fixed-dose tablet formulations of dihydroartemisinin and piperaquine in Vietnamese subjects
Nguyen Trong Chinh
Department of Infectious Diseases, Military Hospital, Hanoi, Vietnam
Antimicrob Agents Chemother 53:828-31. 2009
- Pitavastatin inhibits azoxymethane-induced colonic preneoplastic lesions in C57BL/KsJ-db/db obese mice
Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan
Cancer Sci 101:1701-7. 2010
..Therefore, some types of statins, including pitavastatin, may be a useful chemoprevention modality for colon cancer in obese individuals...
- Mapracorat, a novel selective glucocorticoid receptor agonist, inhibits hyperosmolar-induced cytokine release and MAPK pathways in human corneal epithelial cells
Megan E Cavet
Pharmaceutical R and D, Bausch and Lomb, Inc, Rochester, NY 14609, USA
Mol Vis 16:1791-800. 2010
..This study assessed the anti-inflammatory effects of mapracorat in an in vitro osmotic stress model which mimics some of the pathophysiological changes seen in dry eye...
- Should moxifloxacin be used for the treatment of extensively drug-resistant tuberculosis? An answer from a murine model
Laboratoire de Bacteriologie Hygiene, Faculte de Medecine, Pierre et Marie Curie Université Paris, 91 Boulevard de l Hopital, Paris Cedex 13, France
Antimicrob Agents Chemother 54:4765-71. 2010
- Pharmacokinetics and ex vivo pharmacodynamic antimalarial activity of dihydroartemisinin-piperaquine in patients with uncomplicated falciparum malaria in Vietnam
Dao Van Hoang Nguyen
Department of Infectious Diseases, Military Hospital 175, Ho Chi Minh City, Vietnam
Antimicrob Agents Chemother 53:3534-7. 2009
..Dihydroartemisinin is responsible for most of the ex vivo antimalarial activity of dihydroartemisinin-piperaquine...